The Distribution and Regulation of Aromatase in the Mammalian Brain: from Mice to Monkeys

The mammalian brain produces low levels of estrogens relative to the ovary and placenta, but by restricting synthesis to the site of estrogen action is able to exert powerful effects on neural development and function. The final step in estrogen production is the conversion of androgens to estrogens by cytochrome P450 aromatase. Recent evidence that hippocampus is capable of synthesizing estrogen de novo from cholesterol suggests a new paradigm for mammals in which sex steroids act independently of the gonads to regulate brain functions. In general, aromatase exhibits a dynamic and complex regulation that varies regionally, as well as with an animal's age, sex, and physiologic status. This chapter summaries our current understanding of the distribution and regulation of aromatase in the mammalian brain and describes classic as well as novel functions for local estrogen synthesis in the brain.